Vascular cell adhesion molecule-1 (VCAM-1), a member of the immunoglobulin (Ig) supergene family, is expressed on activated endothelium. The integrin VLA-4 (a.sub.4.beta..sub.1), is the principal receptor for VCAM-1. VLA-4 is expressed on many cell types including circulating lymphocytes, eosinophils, basophils, and monocytes. VCAM-1 also binds to a second integrin LPAM-1 (Peyer's patch adhesion molecule) with is expressed on B and T-cells. The integrin LPAM-1 can also bind with another cell adhesion molecule called mucosal addressing cell adhesion molecule (MadCAM). Binding of the integrins VLA-4 and LPAM-1 to cell adhesion molecules VCAM-1 or MadCAM normally allows the passage of macromolecules and circulating cells from blood to tissue. However, binding of integrins to cell adhesion molecules can result in undesirable inflammation wherein the above cell types infiltrate tissue and cause tissue damage.
Therefore, cell adhesion molecule/integrin antagonists which inhibit the binding of integrins to cell adhesion molecules are able to prevent undesirable inflammation. For example, such antagonists are needed to prevent tissue damage caused by inflammatory bowel disease, T-cell emigration in arthritis, eosinophil accumulation and bronchoconstriction in asthma, and prolongation of the survival time of tissue allografts.